In this revised application for a K01 Mentored Research Scientist Development Award, Dr. Nicole Barbarich-Marsteller has proposed a comprehensive training and research plan in the translational neurobiology of substance abuse and eating disorders. There is significant comorbidity between these disorders and preclinical studies suggest that food restriction increases the reinforcing effects of psychostimulants; however, we are limited by 2 significant gaps in the literature that inhibit the translation of preclinical research on the effects of food restriction on drug reward into a better understanding of the relationship between clinical eating disorders and substance abuse. First, preclinical research has utilized adult rats, whereas the clinical onset of eating disorders and initial drug use typically occurs during adolescence. Second, preclinical research has focused on males, whereas the overwhelming majority of individuals with eating disorders and a significant proportion of substance abusers are females. The fact that there are sex-dependent changes in the dopamine receptor system during adolescence suggests there may be sex differences in the development of vulnerability to addictive behaviors during adolescence. Thus, the research aims of this grant are to use a multi-dimensional approach (conditioned place preference, self-administration, receptor density, microPET imaging) to identify how food restriction alters the behavioral and neurochemical response to psychostimulants during adolescence and to determine whether these effects are sex-dependent. The training goals for Dr. Barbarich-Marsteller are to: 1) acquire a more comprehensive knowledge of substance abuse and reward mechanisms; 2) gain expertise in sex-dependent, developmental aspects of the dopamine system and how they relate to addictive behaviors; 3) expand expertise in preclinical techniques for studying the dopamine system; 4) increase knowledge of the clinical relationship between substance abuse and eating disorders; and 5) increase proficiency in manuscript and grant writing and ethical issues in research. Overall, this award will ensure Dr. Barbarich-Marsteller's successful transition to an independent investigator. PUBLIC HEALTH RELEVANCE: The onset of substance abuse and eating disorders are increased during adolescence, yet the sex-dependent and neurobiological mechanisms that increase vulnerability during this period are not well understood. These studies will fill critical gaps in our understanding of adolescent reward mechanisms.